First-Line PD-1 Blockade, Cisplatin, Paclitaxel Effective for Advanced PSCC in Retrospective Study

Penile squamous cell carcinoma (PSCC) is a rare disease with a poor prognosis. There is a lack of data on first-line (1L) regimens for distant metastatic PSCC, with a 2-year overall survival (OS) rate of just 21%.

As the preferred strategy of combined chemotherapy lacks substantial progression-free survival (PFS) and OS rates, the use of immune checkpoint blockades (ICBs) in conjunction with chemotherapy has been studied for the disease, providing better results for patients. However, this combination has been studied sparingly.

A recent retrospective, multicenter study has analyzed 1L treatment with PD-1 blockades combined with cisplatin and paclitaxel (TP)-based chemotherapy in patients with HR stage IV PSCC to determine the efficacy and safety of the combination treatment.

Data from 32 eligible patients with pathologically confirmed stage IV PSCC who had undergone treatment with PD-1 blockades and chemotherapy between October 2019 and August 2023 were analyzed.

Each patient received tislelizumab 200 mg or torpalimab 240 mg on day 1 of treatment, combined with cisplatin 25 mg/m² on days 1–3 and paclitaxel–based chemotherapy (either albumin-bound paclitaxel 260 mg/m² or paclitaxel 175 mg/m² on day 1) every 3 to 4 weeks for a maximum of 4 to 6 cycles, or until disease progression or unacceptable toxicity.

Objective response rate (ORR) was defined as the proportion of patients who achieved the best response of confirmed complete response (CR) or partial response (PR), while disease control rate (DCR) was defined as the percentage of patients with either CR, PR, or stable disease (SD). Pathologic complete response (pCR) was defined as no residual invasive tumor cells in the resected tumor sites.

The median follow-up was 21.1 months (IQR, 14.1–42.7). A total of 12 (37.5%) patients had previously undergone partial or radical penectomy, while 5 (15.6%) had undergone penectomy combined with inguinal lymph node dissection (ILND), and 2 (6.3%) had received penectomy combined with inguinal plus pelvic lymph node dissection (PLND).

Pelvic lymph node metastases were found in 25 (78.1%) patients, while the remaining 7 (21.9%) had fixed inguinal lymph nodes. Of the patients with metastasis to distant sites, 2 patients had lung metastases and 3 had bone metastases. A total of 21 (65.6%) patients were PD-L1–positive (tumor proportion score [TPS] ≥1%), and 6 patients (18.8%) had a TPS ≥50%.

Each patient received at least 2 cycles of PD-1 blockade with TP-based chemotherapy in the first-line setting, with a median number of 4 treatment cycles. A total of 12 (37.5%) patients were treated with toripalimab plus paclitaxel, ifosfamide, and cisplatin (TIP), and the remaining 20 (62.5%) patients received tislelizumab with TP.

Of the 32 patients, 2 achieved CR and 23 achieved PR, with an ORR of 78.1% (95% CI, 60.0%–90.7%). A total of 6 (18.8%) patients achieved SD for an overall DCR of 96.9% (95% CI, 83.8%–99.9%). One (3.1%) patient experienced progressive disease after 2 cycles of treatment.

Of 27 patients with locally advanced PSCC, 13 (48.1%; including 2 with CR, 10 with PR, and 1 with SD) subsequently received consolidated ILND and PLND, and 6 patients (22.2%; including 2 with CR and 4 with PR) achieved a pCR. Locally advanced disease was linked to a higher ORR than in patients with distant metastasis, but the difference was not statistically significant (85.6% vs 40.0%; P=.06), and the ORRs did not significantly differ among the subgroups.

The median follow-up was 21.1 months (95% CI, 14.1–42.7), and the median PFS and OS were 15 months (95% CI, 11.4–NA) and 19.3 months (95% CI, 16.7–NA), respectively.

The combination of first-line treatment with PD-1 blockade and TP-based chemotherapy proved to be effective and well-tolerate in patients with advanced PSCC.